In 2010, the International Conference on the Reduction of Drug Related Harm shared its 21st birthday with one of its most constant companions: hepatitis C. The co-occurrence of these significant anniversaries provides an opportunity to reflect critically on the formative role played by hepatitis C, and on our responses to it, in the development of harm reduction. The commentary takes an interdisciplinary approach to analyse the implications of a foundational aspect of harm reduction and the response to hepatitis C: medicalisation. It draws on a range of literature and research disciplines to highlight a set of issues poorly visible from within medical expertise. This commentary highlights two trends, both of which emerge from hepatitis C's place as a thoroughly medicalised object. First, hepatitis C has contributed to an increasing emphasis on individual responsibility in prevention initiatives, and second, it has contributed to the homogenisation of affected individuals in relation to treatment. While acknowledging the benefits for injecting drug users that have flowed from the medicalisation of hepatitis C, we note that insufficient attention is sometimes paid to the impact of medical and public health imperatives on the goals and values of harm reduction. We conclude by considering some key ethical and political challenges that harm reduction must confront as it continues to place the status and well-being of drug users at the centre of its rationale and work.